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Communication

Secretion of Mutant DNA and mRNA by the Exosomes of Breast Cancer Cells

by
Olga E. Andreeva
1,
Yuri Y. Shchegolev
1,
Alexander M. Scherbakov
1,*,
Ekaterina I. Mikhaevich
1,
Danila V. Sorokin
1,
Margarita V. Gudkova
1,
Irina V. Bure
2,
Ekaterina B. Kuznetsova
2,
Dmitry S. Mikhaylenko
2,
Marina V. Nemtsova
2,
Dmitry V. Bagrov
3 and
Mikhail A. Krasil’nikov
1
1
Department of Experimental Tumor Biology, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia, 115522 Moscow, Russia
2
Laboratory of Medical Genetics, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
3
Department of Bioengineering, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
*
Author to whom correspondence should be addressed.
Molecules 2021, 26(9), 2499; https://doi.org/10.3390/molecules26092499
Submission received: 27 February 2021 / Revised: 22 April 2021 / Accepted: 22 April 2021 / Published: 25 April 2021
(This article belongs to the Special Issue Targeting of Signaling Pathways for Cancer Therapy)

Abstract

Exosomes are the small vesicles that are secreted by different types of normal and tumour cells and can incorporate and transfer their cargo to the recipient cells. The main goal of the present work was to study the tumour exosomes’ ability to accumulate the parent mutant DNA or RNA transcripts with their following transfer to the surrounding cells. The experiments were performed on the MCF7 breast cancer cells that are characterized by the unique coding mutation in the PIK3CA gene. Using two independent methods, Sanger sequencing and allele-specific real-time PCR, we revealed the presence of the fragments of the mutant DNA and RNA transcripts in the exosomes secreted by the MCF7 cells. Furthermore, we demonstrated the MCF7 exosomes’ ability to incorporate into the heterologous MDA-MB-231 breast cancer cells supporting the possible transferring of the exosomal cargo into the recipient cells. Sanger sequencing of the DNA from MDA-MB-231 cells (originally bearing a wild type of PIK3CA) treated with MCF7 exosomes showed no detectable amount of mutant DNA or RNA; however, using allele-specific real-time PCR, we revealed a minor signal from amplification of a mutant allele, showing a slight increase of mutant DNA in the exosome-treated MDA-MB-231 cells. The results demonstrate the exosome-mediated secretion of the fragments of mutant DNA and mRNA by the cancer cells and the exosomes’ ability to transfer their cargo into the heterologous cells.
Keywords: exosomes; breast cancer cells; DNA transferring; cancer; signalling exosomes; breast cancer cells; DNA transferring; cancer; signalling
Graphical Abstract

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MDPI and ACS Style

Andreeva, O.E.; Shchegolev, Y.Y.; Scherbakov, A.M.; Mikhaevich, E.I.; Sorokin, D.V.; Gudkova, M.V.; Bure, I.V.; Kuznetsova, E.B.; Mikhaylenko, D.S.; Nemtsova, M.V.; et al. Secretion of Mutant DNA and mRNA by the Exosomes of Breast Cancer Cells. Molecules 2021, 26, 2499. https://doi.org/10.3390/molecules26092499

AMA Style

Andreeva OE, Shchegolev YY, Scherbakov AM, Mikhaevich EI, Sorokin DV, Gudkova MV, Bure IV, Kuznetsova EB, Mikhaylenko DS, Nemtsova MV, et al. Secretion of Mutant DNA and mRNA by the Exosomes of Breast Cancer Cells. Molecules. 2021; 26(9):2499. https://doi.org/10.3390/molecules26092499

Chicago/Turabian Style

Andreeva, Olga E., Yuri Y. Shchegolev, Alexander M. Scherbakov, Ekaterina I. Mikhaevich, Danila V. Sorokin, Margarita V. Gudkova, Irina V. Bure, Ekaterina B. Kuznetsova, Dmitry S. Mikhaylenko, Marina V. Nemtsova, and et al. 2021. "Secretion of Mutant DNA and mRNA by the Exosomes of Breast Cancer Cells" Molecules 26, no. 9: 2499. https://doi.org/10.3390/molecules26092499

APA Style

Andreeva, O. E., Shchegolev, Y. Y., Scherbakov, A. M., Mikhaevich, E. I., Sorokin, D. V., Gudkova, M. V., Bure, I. V., Kuznetsova, E. B., Mikhaylenko, D. S., Nemtsova, M. V., Bagrov, D. V., & Krasil’nikov, M. A. (2021). Secretion of Mutant DNA and mRNA by the Exosomes of Breast Cancer Cells. Molecules, 26(9), 2499. https://doi.org/10.3390/molecules26092499

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